Tim-3基因多态性与乙型肝炎病毒感染转归的相关性

目的:研究中国汉族人群T淋巴细胞免疫球蛋白黏蛋白-3(Tim-3)基因标签单核苷酸多态性(tagSNP)rs11741184C/G和rs13170556A/G位点多态性与乙型肝炎病毒(HBV)感染转归的关系.方法:采用SNaPshot技术检测996例慢性乙型肝炎患者及301例急性HBV感染自限性恢复患者Tim-3基因rs11741184和rs13170556tagSNP位点的多态性,计算其基因型和等位基因分布频率及单体型分布频率.结果:Tim-3基因tagSNPrs11741184位点基因型CC、CG、GG在急性乙型肝炎患者中的分布频率分别为84.39%(254/301)、15.28%(46/301)、0.33%(1/301),在慢性乙型肝炎组中分布频率分别为86.04%(857/996)、13.65%(136/996)、0.3%(3/996),两组比较无统计学差异;Tim-3基因tagSNP rs13170556基因型AA、GA、GG在急性乙型肝炎患者中的分布频率分别为68.77%(207/301)、28.57%(86/301)、2.66%(8/301),慢性乙型肝炎组患者中的分布频率分别为68.07%(6...     

Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan

Attention deficit hyperactivity disorder (ADHD) is a common heritable childhood psychiatric disorder. Since methylphenidate, one of the main drugs used to treat ADHD, targets the dopamine transporter, this study examined the linkage disequilibrium (LD) structure of the dopamine transporter gene (DAT1) and investigated whether the DAT1 gene was associated with ADHD. This Chinese family-based association sample consisted of 273 DSM-IV diagnosed ADHD probands and their family members (n = 906). We screened 15 polymorphisms across the DAT1 gene, including 14 single nucleotide polymorphism (SNP) markers and the variable number of tandem repeat (VNTR) polymorphism in 3′-untranslated region (3′UTR). Calculations of pairwise LD revealed three main haplotype blocks (HBs): HB1 (intron 2 through intron 6), HB2 (intron 8 through intron 11), and HB3 (3′UTR). Family-Based Association Tests showed that no allele was significantly more transmitted than expected to the ADHD children for these 15 markers. Haplotype-Based Association Tests showed that a haplotype rs27048 (C)/rs429699 (T) was significantly associated with the inattentive subtype (P = 0.008). In quantitative analyses, this haplotype also demonstrated significant association with the inattention severity (P = 0.012). Our finding of the haplotype rs27048 (C)/rs429699 (T) as a novel genetic marker in the inattentive ADHD subtype suggests that variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.     

云南汉族FZD3基因多态性及其单倍型与精神分裂症关联研究

目的 探讨FZD3基因上中下游三位点rs2241802、rs2323019、rs352203在精神分裂症病理生理机制中的可能作用.方法 采用横断面病例-对照研究.患者组为153例云南汉族精神分裂症患者.正常对照组为与患者组性别、年龄、文化程度匹配的100名云南汉族健康人.对患者组用阳性和阴性症状量表(PANSS)评定病情的严重程度.运用PCR-RFLP技术对FZD3基因的三位点进行多态性检测,并运用连锁不平衡分析,用单因素方差分析比较组间差异.结果 患者组的FZD3基因rs2241802、rs2323019、rs352203位点基因型频率和等位基因频率在精神分裂症患者样本中差异无统计学意义(P＞0.05).汉族样本中rs2241802-rs2323019的D'=0.021,r2=0.000;rs2241802-rs352203的D'=0.033,r2=0.001;rs2323019-rs352203的D'=0.057,r2=0.002,且A-A-C单倍型频率在精神分裂症患者组及对照组间差异有统计学意义(P=0.032),G-A-C单倍型频率在精神分裂症患者组及对照组间差异有统计学意义(P=0.024).患者组的FZD3基因rs2241802、rs2323019、rs352203三位点各个基因型在PANSS量表中各项因子分、总分的相关性均无统计学意义(P＞0.05).结论 FZD3基因rs2241802、rs2323019、rs352203 多态性可能与云南汉族精神分裂症无关,而A-A-C单倍型和G-A-C单倍型可能与云南汉族精神分裂症相关.     

The VEGF +405 G>C 5' untranslated region polymorphism and risk of PCOS: a study in the South Indian Women

Purpose

The aim of this study was to investigate the association between two common single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene (−460C/T and +405G/C) and polycystic ovary syndrome (PCOS) risk in south Indian women.

Methods

This study involves clinically confirmed PCOS patients (n = 126) and non-PCOS controls (n = 130) of south Indian origin (Dravidian linguistic group). Genotyping of the VEGF gene −460C/T and +405G/C SNPs were performed by PCR and sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D'') for pairwise linkage disequilibrium (LD) were assessed by Haploview Software.

Results

The frequencies of +405G/G genotype (P = 0.03) and +405G alleles (P = 0.006) were significantly higher in patients compared to controls. Whereas the genotype and allele frequencies of −460C/T SNP were not significantly different between patients and controls. In addition, LD analysis revealed no significant difference between patients and controls.

Conclusion

Our findings suggest that the VEGF +405G/C polymorphism may constitute an inheritable risk factor for PCOS in south Indian women.     

Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We performed a case-control study of501 Chinese patients with chronic HBV infection and301 self-limiting HBV-infected individuals as controls.Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract highdensity tubes. Tag SNPs were identified using genotype data from the panel(Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6(rs17147230A/T,rs2066992G/T,rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.RESULTS:Five haplotypes were involved in the analysis,with frequencies higher than 0.03. One of the haplotypes,TTAA,was significantly different between the two groups. Overall haplotype P values were:ATAA,P = 0.605,OR(95%CI) = 1.056(0.860-1.297); TGAG,P = 0.385,OR(95%CI) = 1.179(0.813-1.709); TGGG,P = 0.549,OR(95%CI) = 1.087(0.827-1.429); TTAA,P = 0.004,OR(95%CI) = 0.655(0.491-0.873); TTAG,P = 0.266,OR(95%CI) = 1.272(0.832-1.944). However,the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were:rs17147230,P = 0.696,OR(95%CI) = 1.041(0.850-1.276); rs2066992,P = 0.460,OR(95%CI)= 1.090(0.868-1.369); rs2069837,P = 0.898,OR(95%CI) = 0.983(0.759-1.274); rs2069852,P = 0.165,OR(95%CI) = 0.859(0.693-1.064). Overall genotype P values were:rs17147230,P = 0.625; rs2066992,P= 0.500; rs2069837,P = 0.853; and rs2069852,P =0.380.CONCLUSION:The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.     

HLA-B*07 is a high risk allele for familial cervical cancer

Aim: The purpose of this study was to investigate 50 women from eight families with familial cervical cancer in Wufeng County, Hubei Province, China, a region with a high incidence of cervical cancer. Eighty-nine healthy women, of similar age, location and ethnicity, were selected as a control group. Methods: Blood samples were collected from both groups, and HLA-A, HLA-B, and HLA-DRB1 genotypes were profiled with the Multi-Analyte Profiling system (xMAP) (Luminex HLA-SSO) using a WAKFlow HLA typing kit. Results were analyzed with Luminex HLA typing software and showed good stability, reproducibility and specificity. Results: We found several high risk alleles in women with familial cervical cancer, that associated with the highest risk being HLA-B*07 (OR = 8.7, 95% CI = 1.8-41.1). Conclusions: HLA-B*07 is a high risk allele for cervical cancer, and has strong potential for use as a molecular biomarker.     

Association between HLA-DQ genotypes and haplotypes vs Helicobacter pylori infection in an Indonesian population

Background: Helicobacter pylori is an important gastrointestinal pathogen related to the development ofnot only atrophic gastritis and peptic ulcer, but also gastric cancer. Human leukocyte antigens (HLA) may playparticular roles in host immune responses to bacterial antigens. This study aimed to investigate the associationbetween HLA-DQA1 and DQB1 genotypes and haplotypes vs H. pylori infection in an Indonesian population.Methods: We selected 294 healthy participants in Mataram, Lombok Island, Indonesia. H. pylori infectionwas determined by urea breath test (UBT). We analyzed HLA-DQA1 and DQB1 genotypes by PCR-RFLPand constructed haplotypes of HLA-DQA1 and DQB1 genes. Multiple comparisons were conducted accordingto the Bonferroni method. Results: The H. pylori infection rate was 11.2% in this Indonesian population. TheDQB1*0401 genotype was noted to be associated with a high risk of H. pylori infection, compared with theDQB1*0301 genotype. None of the HLA-DQA1 or DQB1 haplotypes were related to the risk of H. pylori infection.Conclusions: The study suggests that HLADQB1 genes play important roles in H. pylori infection, but there wasno statistically significant association between HLA-DQA1 or DQB1 haplotypes and H.pylori infection in ourLombok Indonesian population.     

Haplotype Analysis of MDR1 and Risk for Cervical Cancer in Northeastern Thailand

Objective: The aim of this study was to investigate the association between genotype and haplotype of MDR1 (C1236T, G2677T/A and C3435T) and the risk for cervical cancer in Northeastern Thai women. Methods: An age-matched case-control study involving squamous cell cervical cancer (SCCA) patients (n=204) and healthy controls (n=204) was enrolled for MDR1 genotyping by real-time PCR method. Results: The genotype distribution of MDR1 in both patients and controls was not significantly different (p>0.05). The haplotype analysis showed that T-T-T was the most common haplotype in this population. Significantly increased risk of cervical cancer was observed in carriers of T-T-C and C-G-T haplotypes with ORs of 1.86 (95%CI=1.02-3.39, p=0.0416) and 2.00 (95%CI=1.18-3.40, p=0.0140), respectively. Analysis of 2677-3435 haplotype showed increased risk for cervical cancer in G-T (OR=1.55; 95% CI=1.12-2.13, p=0.0432) and T-C (OR=1.91; 95%CI=1.05-3.47, p=0.0325). Conclusion: The results provide evidence that haplotype of MDR1 may be an important risk factor for cervical cancer development in Northeastern Thai women.